Omega-3 fatty acids (n-3 FAs) are believed to reduce risk for cardiovascular disease (CVD), especially sudden cardiac death, and for congestive heart failure (CHF). The epidemiology, however, remains conflicted, and the mechanisms by which dietary n-3 FAs operate remain speculative. A decrease in heart rate, an increase in heart rate variability, and improved endothelial function have all been associated with higher levels of n-3 FA biomarkers. These may be mediated by changes in membrane structure/function and/or eicosanoids or cytokine- induced inflammatory proteins. Red blood cell (RBC) n-3 FA content has recently been shown to be a valid surrogate biomarker of human myocardial n-3 FA levels. In addition to being more objective (relative to dietary questionnaire-based measures), RBC n-3 FAs may be preferable to plasma levels of FAs because they reflect tissue FA levels over several weeks and are less variable (analogous to hemoglobin A1C in the assessment of average blood glucose levels). No prior studies have evaluated the relationships between RBC n-3 FAs (or FA patterns) on cardiovascular outcomes and vascular risk markers. To address these gaps in knowledge, we propose to measure RBC FA composition in two Framingham Heart Study cohorts (the Offspring Study and the minority, Omni Study). The RBC n-3 FA content will be analyzed in conjunction with the rich dataset already collected on these subjects which includes classical and emerging risk factors, subclinical left ventricular (LV) remodeling, vascular stiffness, and endothelial function. These subjects are also under continuous surveillance for the development of CVD and CHF. We propose the following 3 aims: Aim 1. RBC n-3FAs and clinical correlates. To define the cross-sectional clinical correlates, the heritability and the stability of RBC n-3 FA content in a community-based sample. Aim 2. RBC n-3 FAs and vascular &ventricular remodeling. To examine the cross-sectional relations of RBC n-3 FAs to a) microcirculatory function and conduit artery stiffness (using tonometry), b) endothelial function (using ultrasound-based brachial artery flow-mediated dilation), and c) indexes of LV remodeling (using echocardiography). Aim 3. RBC n-3 FAs and the development of CVD risk factors &incident CVD. To investigate prospectively the relations of RBC n-3 FA content to longitudinal tracking of the evolution of CVD risk factors and of the incidence of CVD events. These data will not only inform future studies assessing the predictive value of RBC FAs for CVD, but also for other diseases (e.g., dementia, arthritis, macular degeneration, etc.) potentially modulated by these FAs. PUBLIC HEALTH RELEVANCE: There has been increasing interest in the heart-healthy effects of fish oils, especially the omega-3 fatty acids (EPA and DHA) that they contain. While we now know that giving fish oil supplements to people who are at high risk for heart attacks seems to reduce their risk for heart disease, we don't know how these natural oils work to help the heart, nor do we know the degree to which normal variations in blood levels are related to heart disease risk factors. This study will attempt to uncover heretofore unknown links between blood omega-3 levels and such things as how fast people develop high blood pressure, how flexible (i.e., healthy) the blood vessels are, how vigorously the heart pumps blood, or how inflamed the arteries are. All of these factors are important in determining risk for heart attacks and strokes, and so learning how they are affected by omega-3 fatty acids will help us devise new treatment strategies to reduce risk for these major diseases in the US.